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ISSN: 2320-5407 Int. J. Adv. Res.

7(4), 1274-1281

Journal Homepage: - www.journalijar.com

Article DOI: 10.21474/IJAR01/8950


DOI URL: http://dx.doi.org/10.21474/IJAR01/8950

RESEARCH ARTICLE

“CORRELATION OF CORRECTED QT INTERVAL WITH QUANTITATIVE CARDIAC TROPONIN-I


LEVELS AND ITS PROGNOSTIC ROLE IN NON ST ELEVATION MYOCARDIAL INFARCTION.

Routray S. N.1, Satapathy M. K.2, Mohanty N. K3, Satpathy C.3 and Dash B. K4.
1. Professor, Dept.of Cardiology, S.C.B Medical College, Cuttack, Odisha, India.
2. Senior Resident, Dept.of Cardiology, S.C.B Medical College, Cuttack, Odisha, India.
3. Asso. Professor, Dept.of Cardiology, S.C.B Medical College, Cuttack, Odisha, India.
4. Asst. Professor, Dept.of Cardiology, S.C.B Medical College, Cuttack, Odisha, India.
……………………………………………………………………………………………………....
Manuscript Info Abstract
……………………. ………………………………………………………………
Manuscript History Background: There is a large body of evidence of specific myocardial
Received: 22 February 2019 injury markers such as cardiac troponin I (cTnI) and cardiac troponin T
Final Accepted: 24 March 2019 (çTnT) for short and long-term prognostic values of NSTE-ACS
Published: April 2019 mortality and new infarction. Objective: The present study was
conducted to assess the correlation between corrected QT interval with
cardiac troponin-I levels in NSTE-MI patients and to assess if
prolonged corrected QT interval independently predicts higher 30-day
Major Adverse Cardiac Events (MACE) in NSTE-MI patients.
Material and Method: we enrolled 301 patients with the diagnosis of
NSTEMI. Demographic variables at admission were age, gender,
arterial pressure, history of CAD, hypertension, diabetes mellitus,
smoking, dyslipidemia, previous coronary revascularization, and
medication before entering the study. All patients were classified at
admission according to the TIMI score for NSTE-ACS.Cardiac
troponin I was measured in all cases with the sample collected 24 hr
after the beginning of last angina episode. Concentrations ≥ 0.01 ng/ml
were considered to be positive. A second measurement was done after
12 h in patients in whom the first determination is negative.Corrected
QT interval(longest) measurement was done according to American
Heart association guidelines. Patients were treated as per protocol.
Major adverse cardiovascular events (includes, death due to
cardiovascular cause, Non-fatal Myocardial Infarction and Recurrent
Unstable Angina and ensuing urgent revascularization.) that were
observed up to 30 days post discharge. Results: Troponin-I values and
QTc interval was significantly higher in patients with diabetes and
dyslipidemia, who presented with higher TIMI scores, severe LV
systolic dysfunction ,higher killip class and hypotension and with
multivessel disease, did not differ significantly according to culprit
vessel. There was significant correlation with coefficient of 0.637
between QTc-max and Troponin I.Patients with MACE had
significantly higher mean Troponin - I and mean QTc interval.
Conclusion: Corrected QT interval has a strongly positive significant
correlation with quantitative troponin I level in NSTEMI patients and
Prolonged corrected QT interval is independently predictive of higher

Corresponding Author:-Routray S. N.
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Address:-Professor, Dept.of Cardiology, S.C.B Medical College, Cuttack, Odisha, India.
ISSN: 2320-5407 Int. J. Adv. Res. 7(4), 1274-1281

rate of major adverse cardiovascular events after NSTEMI within 30


days post discharge.
Copy Right, IJAR, 2019,. All rights reserved.
……………………………………………………………………………………………………....
Introduction:-
The latest American College of Cardiology and the American Heart Association (ACC/AHA) and European Society
of Cardiology (ESC) guidelines recognize the importance of early risk stratification in the management of NSTE-
ACS and recommend an integrated approach to risk assessment. The information required for this assessment is
derived from the patient’s history and physical examination, electrocardiogram (ECG) and cardiac biomarkers. 1,2

It has been shown that the corrected QT interval prolongation is an independent risk marker in NSTE-ACS
.However, there is scarce information about its relationship with other variables of known prognostic value, such as
cardiac troponins.

There is a large body of evidence of specific myocardial injury markers such as cardiac troponin I (cTnI) and cardiac
troponin T (çTnT) for short and long-term prognostic values of NSTE-ACS mortality and new infarction.3-6

Several studies have been published showing the prolonged corrected QT interval (QTc) in 12 lead ECG as an
independent risk marker in NSTE-ACS with or without acute ischemic changes, both at 30-day post-discharge or
long-term followup.7-9

Aims and objectives:-


1)To assess the correlation between corrected QT interval and cardiac troponin-I levels in NSTE-MI patients. 2) To
assess if prolonged corrected QT interval independently predicts higher 30-day Major Adverse Cardiac Events
(MACE) in NSTE-MI patients.

Methods:-
Patients with NSTEMI ( defined as abnormal cardiac Troponin I ≥ 0.01 ng/ml)was included in the study . A standard
ECG recorded, at admission then at 6hr, 12hr, 24hr and 48hr post-admission. Blood samples were obtained at
admission for complete blood count, serum urea, creatinine, electrolytes, A Fasting lipid profile was also done
within 24 hrs of admission. Upon admission to the hospital all patients received conventional treatment according to
existing departmental protocol.

Demographic variables at admission registered were age, gender, arterial pressure, history of CAD, hypertension,
diabetes mellitus, smoking, dyslipidemia, previous coronary revascularization, and medication before entering the
study. After basal characterization and TIMI scoring 10, all patients were followed-up for 30 days after discharge.

QT interval measurement was done according to American Heart association guidelines. , maximum interval taken
in the ECG within 48h post admission. AHA linear regression formula was used to calculate QTc according to
HR.11,12 Corrected QT(QTc)= Observed QT +1.75(observed HR-60)

Cardiac troponin I was measured with the sample collected 24 hr after the beginning of last angina episode. A
second measurement was done after 12 h in patients in whom the first determination is negative
Major adverse cardiovascular events (MACE) that were observed up to 30 days post discharge were death due to
cardiovascular cause, Non-fatal Myocardial Infarction (defined by increased cardiac biomarkers, characteristic
dynamic and evolving electrocardiographic changes. and prolonged chest discomfort), and Recurrent Unstable
Angina and ensuing urgent revascularization. Patients were divided into two groups according to the presence
(group A) or absence (group B) of MACE.

Inclusion criteria:
Male and female patients, more than 18 years of age, admitted with diagnosis of Non-ST elevation myocardial
infarction, with or without acute ischemic ECG changes.
Exclusion criteria:
1.ST-segment-elevation-AMI,Unstable Angina-ACS. 2.Flat T wave (< 1 mm),Wide QRS, Ventricular hypertrophy
3.Serum potassium ≤ 3.5.meq/I or > 5.5 meq/L,Serum calcium <8.5 mg/dl or > 10.5 mg 4.Severe valvular disease or

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cardiomyopathy 5.Patients receiving antiarrhythmic or QT interval modifying drugs 6. Wolff-Parkinson-White


abnormality, atrial fibrillation, atrial flutter or frequent extrasystoles (> 10/min)

Statistical analysis:
Continuous variables with normal distribution were expressed as mean ± standard deviation (SD) and continuous
variables with non-normal distribution were expressed as median (interquartile range). Unpaired Student’s t test was
used to compare continuous variables, and Chi square test was used to compare continuous variables, as appropriate.
Spearman’s correlation test was employed to establish the correlation between troponin-I level and QTc max values.
Multivariate logistic regression analysis was performed to identify independent predictors of MACE.

Ethic Statement:
Study procedure was approved by Institutional Ethics Committee of S.C.B. Medical college and
Hospital,Cuttack,Odisha(Regd.No ECR/84/Inst/OR/2013)while grant for the study was approved by the institutional
Review Board vide Ref.No.766/15.1.2019.Written consent was sorted prior to participation from respondents by
means of informed consent.

Results:-
Mean age of the patients was 54.2 ±12.3 years. 212 (70.4%) were males and 89 (29.6%) were females. Mean age of
male and femals patients was 52.2±12.4 years and 58.8±10.7 years, respectively.Maximum no of patients 172
(57.1%) patients were in 46-70 years age group.
AGE GROUP NO. OF PATIENTS PERCENTAGE
<45 YEARS 90 29.9
46-70YEARS 172 57.1
>70 YEARS 39 13.0
TOTAL 301 100.0

Maximum no patients 158 (52.5%) were either active smokers or had stopped smoking in past six months, 113(37
.5%) patients were diabetics and 102 (34%) had a history of hypertension. 63(20.9%) patients had history of CAD
and dyslipidemia was present in 108 (36%) patients
RISK FACTOR TOTAL PERCENTAGE
DIABETES 113 37.5
HYPERTENSION 102 34
CAD 63 20.9
SMOKERS 158 52.5
DYSLIPIDEMIA 108 36

Mean value of maximum troponin I levels in total sample population was 3.53 ± 2.88 ng/ml. Mean value was not
significantly different between male( 3.73 ± 2.96 ng/ml, ) and female sex(3.06 ± 2.65 ng/ml,). (p = 0.06)and was not
significantly different according to age groups. (p>0.1).

Mean Troponin I value was significantly higher in patients with diabetes 4.12 ± 3.14 ng/ml, vs patients without
diabetes 3.17 ± 2.66 ng/ml (P=0.006)and in patients with dyslipidemia 3.84 ± 3.05 ng/ml, vs patients without
dyslipidemia,3.09 ± 2.58 ng/ml (p = 0.02).

Mean Troponin I value varied significantly according to TIMI score,SBP, Killip classes,LVEF. Mean value was
lowest (2.9 ± 2.6 ng/ml )in TIMI 0-2 group (p = 0.01), and highest ( 5.9 ± 2.7 ng/ml) in TIMI 5 -7 group (p <0.01).
Mean value was highest at 6.07 ± 2.56 ng/ml in SBP <90 mm Hg group lowest at 3.10 ± 2.69 ng/ml in SBP 90-140
mmHg group (p<0.01). Mean value was 3.01±2.59 ng/ml in Killip class I group (p<0.01) and 6.11±2.88 ng/ml in
Killip class higher than I group( p<0.001).Mean value was highest at 6.37±2.41 ng/ml in LVEF <35 % group
(p<0.01),and lowest at 1.49±0.75 ng/ml in LVEF >50% group (p<0.01),respectively.

Patient Profile & Trop-I Level


PATIENT PROFILE MEAN TROP I LEVEL (ng/ml)
18-45yrs 3.38 ± 3.03
46-70yrs 3.49 ± 2.78

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AGE (in years) >70yrs 4.06 ± 2.98


PRESENT 4.12 ±3.14
DIABETES ABSENT 3.17 ± 2.66
PRESENT 3.56 ± 2.95
HYPERTENSION ABSENT 3.5 ± 2.81
PRESENT 3.84 ± 3.05
DYSLIPIDEMIA ABSENT 3.09 ± 2.58
PRESENT 3.72 ± 3.08
SMOKING ABSENT 3.15 ± 2.42
PRESENT 3.33 ± 2.84
CAD ABSENT 3.58 ± 2.90
0-2 2.90 ± 2.60
3-4 3.70 ± 2.90
TIMI SCORE 5-7 5.90 ± 2.70
<90 6.07 ± 2.56
SYSTOLIC BLOOD PRESSURE 90-140 3.10 ± 2.69
(mmHg) >140 3.85 ± 3.04
1 3.01 ± 2.59
KILLIP CLASS >1 6.11 ± 2.88
<35 6.37 ± 2.41
LVEF(%) 35-50 2.49 ± 2.28
>50 1.49 ± 0.75

Mean value of maximum QTc interval in total population was 472.31±28.65ms. and did not differ significantly
between male patients (471.9±28.6ms), and female patients (473.3± 28.7ms) p=0.7. Mean valueQTc, in age group
of less than 70 years was 470.81 ± 28.78 ms which was significantly lower than mean value in more than 70 year
age group, 482.41 ± 25.94 ms, (p = 0.018).

Mean corrected QT interval was significantly higher in patients with diabetes 478.74 ± 30.29ms, compared to
patients without diabetes 468.45 ± 26.97ms(p = 0.002) and with dyslipidemia 475.24±29.96ms,compared to patients
without dyslipidemia 466.52 ± 26.07 ms (p=0.014), did not differ significantly among patients with or without
hypertension, history of smoking, and history of CAD.

Mean value was lowest at 463.58 ± 26.16 ms, in TIMI 0 -2 group (p <0.001), and highest at 504.31 ± 21.78 ms, in
TIMI 5 -7 group (p <0.001), respectively. Mean value was lower at 470.65 ± 28.05 ms, in SBP ≥ 90 mmHg group,
and higher at 498.41 ± 25.88 runs in SBP <90 mmHg group (p <0.001), respectively. Mean value was lower at
468.22 ± 27.43 ms, in Killip class 1, and higher at 492.38 ± 26.19 ms in Killip class > 1 group (p < 0.001). . Mean
value was lower at 469.09 ± 28.15 ms, in LVEF ≥ 35% group, and higher at 490.15 ± 24.81ms in LVEF < 35%
group (p <0.001), respectively.

Patient Profile And Corrected Qt Interval


PATIENT PROFILE MEAN QTc MAX (ms)
AGE(in years) <70 470.81 ± 28.78
>70 482.42 ± 25.94
DIABETES PRESENT 478.74 ± 30.29
ABSENT 468.45 ± 26.97
HYPERTENSION PRESENT 473.33 ± 28.77
ABSENT 471.11 ± 28.57
DYSLIPIDEMIA PRESENT 475.24 ± 29.96
ABSENT 466.52 ± 26.07
SMOKING PRESENT 472.89 ± 28.76
ABSENT 471.17 ± 28.55
CAD PRESENT 472.53 ± 29.27
ABSENT 472.25 ± 28.55

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TIMI SCORE 0-2 463.58 ± 26.16


3-4 475.17 ± 28.03
5-7 504.31 ± 21.78
SYSTOLIC BLOOD PRESSURE <90 498.41 ± 25.88
(mmHg) ≥90 470.65 ± 28.05
KILLIP CLASS I 468.22 ± 27.43
>I 492.38 ± 26.19
LVEF (%) <35 490.15 ± 24.81
≥35 469.09 ± 28.15

Maximum patients have single vessel disease i.e 181(60.1%) out of which 114 (62.9%) patients had Left anterior
descending artery (LAD) ,24 (13.2%) patients had Left circumflex artery (LCX) and Forty three (23.7%) patients
had Right coronary artery (RCA) as culprit vessel. Multivessel disease with significant lesion in vessel other than
culprit artery was found in 101 (33.5%) patients. Out of which 51(50.5%) patients had LAD ,Seventeen (16.8%)
patients had LCX and 26(25.7%) patients had RCA as the culprit vessel. Nineteen (6.3%) patients had either non
significant CAD or normal angiogram and 14 patients (13.9%) had significant Left Main disease . Culprit vessel
could not be identified in 7 patients (6.9%) as more than 1 vessel was critically diseased
VESSEL INVOLVED IN CAG NO. OF PATIENTS PERCENTAGE
SINGLE VESSEL DISEASE 181 60.1
MULTI VESSEL DISEASE 101 33.5
NORMAL CORONARIES 19 6.3

Mean Troponin-I value was significantly higher in patients with multivessel disease 4.14 ± 3.20 ng/ml vs single
vessel disease on angiogram 3.17±2.62ng/ml(p<0.005)

TROP I LEVEL (ng/ml)


AVG. 3.53

MVD 4.14

SVD 3.17

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5


Mean corrected QT interval was significantly higher in patients with multivessel disease (478.16 ± 30.50 ms), vs
single vessel disease on angiogram 468.89 ± 26.02 ms (p =0.009).

QTc MAX AND CAD


480 478
475 472
470 468
465
460
Total Sample MV-CAD** SV-CAD**
The Spearman correlation coefficient of 0.637 between QTc-max and Troponin- I, (p <0.001).

Mace
MACE has occurred in 77 out of 301 patients (25.6%) within 30 days follow-up after hospital discharge. These
patients were classified into Group A. Out of these patients, 14/301 (4.6%) patients expired, including 3 cases of
sudden cardiac death, 22/301 (7.3%) patients had suffered recurrent MI. Forty one out of 301 (13.6%) patients
suffered Unstable Angina requiring revascularization within 30 days. The 224 out of 301 (74.4%) patients who did
not suffer MACE within 30 days post discharge, were classified into Group B.
MACE EVENTS NO. OF PATIENTS PERCENTAGE

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DEATH 14 18.18
MYOCARDIAL INFARCTION 22 28.57
URGENT REVASCULARISATION 41 53.24

Group A patients were significantly older (60.19 ± 11.64 years) compared to group B(52.13 ± 11.9 years) (p
<0.001). Proportion of males was significantly more in Group B, 167 (74.6%) vs 45 (58.4%) in group A (p
0.007).Diabetes was significantly more frequent in Group A, 40 (51.9%) patients vs 73 (32.6%) in group B (p =
0.004). Dyslipidemia, Hypertension, Smoking, and history of CAD did not differ significantly among group A and B
patients. Group A patients had significantly higher mean Troponin I level 4.62 ± 3.01 ng/ml, compared to group B
patients, 3.16 ± 2.74 ng/ml (p < 0.001). and significantly higher mean corrected QT interval 482.16 ± 27.23 ms,
compared to group B patients, 468.93 ± 28.41 ms (p < 0.00 1).

MACE AND TROP I LEVEL

Group B

Mean Troponin I Level (ng/ml)**


Group A

0 1 2 3 4 5

MACE AND QTc MAX

Group B 482.1

Mean QTc Max (ms)**


Group A 468.9

460 465 470 475 480 485


In multivariate analysis of a logistic regression model with variables with p < 0.05, TIMI score > 2 (OR 9.9, p
<0.001, 95% CI 3.90-25.52) was the strongest independent predictor for MACE followed by QTc > 468 ms (OR 2.6,
p = 0.018, 95% CI 1.38-5.09) after adjusting for other variables. Troponin I, age, sex, diabetes, SBP <90 mmHg,
Killip class higher than 1, LVEF <35%, and MV-CAD were not independent predictors of MACE.
.
Discussion:-
Troponin I levels correlated significantly with poor prognostic markers in ACS. Highest quartile of troponin I values
was seen in patients who presented with higher TIMI scores, severe left ventricular systolic dysfunction ,higher
killip class and hypotension. (similar to study by lindahl et al,) .In our study, Mean Troponin I value was also
significantly higher in patients with multivessel disease on angiogram (P=0.005) with respect to single vessel
disease group, and did not differ significantly according to culprit vessel.

In FRISC II study, Troponin T levels did not correlate with severity of underlying coronary artery disease on
angiography 13 But in recent studies in stable CAD patients high sensitivity troponin increases with number of
vessels with significant stenosis, as well as number of significant stenosis. 14
Mean QTc interval did not differ significantly between male and female ±patients but varied significantly according
to patient’s age, with age ( < 70 years, mean QTc was significantly lower, p = 0,01 ). with diabetes, p<0.001 or
dyslipidemia (p<0.001).
Mean QTc varied significantly according to TIMI score, killip class, systolic BP and left ventricular ejection fraction
at presentation, with highest value in TIMI 5-7 group(p<0.001), killip class >1,(p<0.001),SBP<90mm Hg and LVEF
<35%( p<0.001)

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Multivessel disease have higher Mean QTc value compared to single vessel disease (p=0.009).The QTc values did
not differ according to culprit vessel.Our finding were comparable from the study published by Jimenez –Candil et
al in NSTEACS patients ,

There was significant correlation between QTc Max and Troponin I level with a correlation coefficient of 0.637
between QTc-max and Troponin I, (p <0.001).

On multivariate analysis, Troponin I level was independently predicted by, Age group (p=0.04), LVEF (p <0.001),
and TIMI score (p < 0.001), after adjusting for sex, diabetes, dyslipidemia , Killip class, SBP, ST deviation, and
MV-CAD. Maximum QTc interval was independently predicted by LVEF (p < 0.001) and TIMI score (p<0.001),
after adjusting for all other variables.

Patients with MACE had significantly higher mean Troponin - I level higher mean QTc interval (p<0.001).

Mueller et al 15,Lindahl et al13 showed that the risk of in hospital and long term mortality increased with absolute
level of troponin-T.According to Gadaleta et al,9Susan et al (reported QTc>0.458)16, Jimenez Candil et al17 the QTc
interval was found to be an independent predictor of MACE risk in NSTEACS population.

Limitation:
This was a relatively small study sample, with even smaller number of patients in various subgroups, therefore a
larger cohort of patients is required to further validate these results.

High sensitivity troponin assays are not widely available. Use of high sensitivity assays instead of conventional
assay might affect the result of predictive model in multivariate analysi and long term follow up assessment of
MACE is advisable.

Conclusion:-
Corrected QT interval has a strongly positive significant correlation with quantitative troponin I level in NSTEMI
patients. Prolonged corrected QT interval is independently predictive of higher rate of major adverse cardiovascular
events after NSTEMI within 30 days post discharge.

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